成骨细胞和破骨细胞衰老改变及其在增龄性骨丢失中的作用

背景认识增龄过程中成骨细胞和破骨细胞变化规律,特别是高龄人群成骨细胞和破骨细胞的生物学特点,对骨质疏松有效合理的防治具有十分重要的意义.目的回顾关于成骨细胞和破骨细胞数量和活性增龄变化的实验及临床研究结果,明确增龄过程中成骨细胞和破骨细胞的变化规律和衰老特点.数据来源1995/2003 PubMed,2002/2004年万方数据库,本实验室研究结果.数据提取PubMed 16篇,万方数据库1篇,本实验室数据.主要观察指标细胞数量、酶活性、基因表达水平.结果高龄人群成骨细胞骨形成作用和破骨细胞骨吸收作用对骨骼的影响都逐渐下降,但表现出不同的特点.①骨形成功能持续降低,主要表现为成骨细胞分裂增生能力降低、基质合成减少、对钙凋激素的敏感性降低.这些变化与骨髓中前体细胞的快速减少有关,使高龄人群骨骼中成骨细胞群由于缺乏新生细胞的不断补充而功能退化.②骨吸收功能短暂激活,主要表现为破骨细胞数量一度增加,而其泌酸和蛋白酶功能基本得以保持.③成骨细胞调节能力降低,主要表现为成骨细胞中RANKL和OPG表达失偶联.结论破骨细胞激活的机制和破骨细胞二次活跃产生不同骨平衡的意义值得探讨.作为建议,作者提倡在基础领域重视骨髓微环境中前体细胞分化增殖的研究.

Senility changes of osteoblasts and osteoclasts and their role in aging bone loss

BACKGROUND: The recognition of change regulation of osteoblasts and osteoclasts in the aging process, especially the biological features of osteoblasts and osteoclasts in elderly population, has quite a significant meaning for the effective and reasonable prevention of osteoporosis.OBJECTIVE: To review the experimental and clinical research result on the number and age-related activity changes of osteoblasts and osteoclasts, and to ensure the regulation and senile features of osteoblasts and osteoclasts in the duration of aging.DATA SOURCE: Articles were obtained from PubMed from 1995 to 2003,and Wanfang data base from 2002 to 2004 and study results from our laboratory.DATA EXTRACT: Sixteen PubMed articles and one from Wanfang data base, as well as data from our laboratory.MAIN OUTCOME MEASURES: Cell number, activity of enzyme andgene expression level.RESULTS: Osteoblasts and osteoclasts changed with different features in the elderly population, although their influences on bone formation and bone redecreased continuously, which presented as: decrease of cell division and proliferation ability, decrease of matrix synthesis, and weak sensibitity to Ca-regulated hormones. These changes are related with the rapid decrease of precursors in bone marrow, which caused functional deterioration due tothe tion of bone resorption function, presented as the temporary increase of osteoclasts number and mostly maintenance of its function of excreting acid and by the uncoupling of receptor activator receptor(RANKL) and osteoprotegrin (OPG)expression.CONCLUSION: The significance of activation mechanism and different bone balance caused by second flurish of osteoclasts deserves exploration. It is suggested by the author that, more attention should be paid in the basic field of precursor differentiation and proliferation in the microenvironment of bone marrow.